Clinical Characteristics of EGPA Patients in Comparison to GPA Subgroup with Increased Blood Eosinophilia from POLVAS Registry.

Objective: To characterize the eosinophilic granulomatosis with polyangiitis (EGPA) population from the POLVAS registry depending on ANCA status and diagnosis onset, including their comparison with the granulomatosis with polyangiitis (GPA) subset with elevated blood eosinophilia (min. 400/µl) (GPA HE) to develop a differentiating strategy. Methods: A retrospective analysis of the POLVAS registry. Results: The EGPA group comprised 111 patients. The ANCA-positive subset (n = 45 [40.54%]) did not differ from the ANCA-negative one in clinics. Nevertheless, cardiovascular manifestations were more common in ANCA-negative patients than in those with anti-myeloperoxidase (MPO) antibodies (46.97% vs. 26.92%, p = 0.045). Patients diagnosed before 2012 (n = 70 [63.06%]) were younger (median 41 vs. 49 years, p < 0.01), had higher blood eosinophilia at diagnosis (median 4,946 vs. 3,200/µl, p < 0.01), and more often ear/nose/throat (ENT) and cardiovascular involvement. GPA HE comprised 42 (13.00%) out of 323 GPA cases with reported blood eosinophil count. Both GPA subsets had a lower prevalence of respiratory, cardiovascular, and neurologic manifestations but more often renal and ocular involvement than EGPA. EGPA also had cutaneous and gastrointestinal signs more often than GPA with normal blood eosinophilia (GPA NE) but not GPA HE. The model differentiating EGPA from GPA HE, using ANCA status and clinical manifestations, had an AUC of 0.92, sensitivity of 96%, and specificity of 95%. Conclusion: Cardiovascular symptoms were more prevalent in the ANCA-negative subset than in the MPO-ANCA-positive one. Since EGPA and GPE HE share similarities in clinics, diagnostic misleading may result in an inappropriate therapeutic approach. Further studies are needed to optimize their differentiation and tailored therapy, including biologics.

Miliary Tuberculosis as Postmortem Diagnosis in Solid Organ Transplant Recipient: Case Report and Review of the Literature.

BACKGROUND: The diagnosis of tuberculosis (TB) in solid organ transplant (SOT) recipients presents challenges that may lead to treatment delay. These include atypical clinical presentations, increased likelihood of negative tuberculin skin test or/and interferon-gamma release assays, and negative sputum smear results despite active disease. The treatment poses challenges due to pharmacokinetic interactions, allograft-related toxicity, and inadequate immune response. CASE REPORT: We report the case of a 70-year-old man after kidney transplantation in 2012. The patient was transferred from the urology unit with deteriorating renal function and presumed urosepsis. His pulmonary chest X-ray showed hilar pulmonary infiltrates. Computed tomography of the chest/abdomen/pelvis revealed mediastinal lymphadenopathy, pulmonary infiltrates, pulmonary effusion, and splenomegaly. His blood results showed pancytopenia and high inflammatory and renal markers. He was treated with broad-spectrum antibiotics covering bacterial, fungal, and viral infections. Despite initial clinical improvement, his kidney function deteriorated, and he required hemodialysis. His temperature continued to spike. On physical examination, he was confused and lethargic. He was scheduled to have a mediastinoscopy with lymph node biopsy, but he died the day before. The postmortem examination revealed miliary tuberculosis with tuberculosis of many organs: kidney transplant, native kidney, bone marrow, mediastinal lymph nodes, lungs, and spleen. CONCLUSIONS: The diagnosis of active TB in transplant recipients requires a high index of suspicion and invasive procedures. The majority of all cases of active TB after SOT are disseminated or occur at extrapulmonary sites. Only a small minority of patients have classic cavitary changes on pulmonary imaging.

Chemokines and Cytokines Profiles in Patients with Antineutrophil Cytoplasmic Antibodies-Associated Vasculitis: A Preliminary Study.

The damage to small vessels in AAV and inflammatory reactions are accompanied by the release of various chemokines and cytokines. Using a flow cytometry technique, we assessed the levels of specific cytokines, namely IL-1ß IL-6, IL-8, IL-10, IL12p70, and TNF, and chemokines, IFN-α, IP-10, and MIG in the serum from 9 healthy volunteers and 20 AAV patients, where 11 of the patients were not treated and evaluated at the time of diagnosis and 9 were already diagnosed and taking CY + GCS. The obtained results were then compared considering the activity of the disease, the type and titre of the ANCA antibodies, the inflammatory status, and the kidneys' condition. Amongst others, the IL-6, IL-8, IL-10, TNF, and MIG levels were much higher in the serum of AAV patients than in healthy controls, whereas the level of IL-1ß was higher in healthy volunteers. Additionally, the levels of IL-6, IL-10, IP-10, and MIG negatively correlated with the eGFR level, while the level of IFN-α positively correlated with the titre of PR3-ANCA. As most of the molecules are implicated in trafficking primed neutrophils towards small vessels, looking for links between the levels of these cytokines/chemokines and the clinical symptoms of AAV may facilitate the diagnosis and predict the progression of the disease.

Respiratory involvement in antineutrophil cytoplasmic antibody-associated vasculitides: a retrospective study based on POLVAS registry.

OBJECTIVES: The study aimed to characterise the Polish population of (ANCA)-associated vasculitides (AAV) with respiratory involvement (RI), in comparison to the subgroup without lung manifestations and the other cohorts. METHODS: Retrospective analysis of the Polish population of AAV with RI was conducted, based on data from the POLVAS registry. Standard descriptive statistics, χ2 test, and Mann-Whitney U test were used to perform comparisons. RESULTS: Among 461 cases qualified to this study, there were 316 cases with RI (68.5%), 206 with granulomatosis with polyangiitis (GPA) (65.2%), 80 with eosinophilic granulomatosis with polyangiitis (EGPA) (25.3%) and 30 with microscopic polyangiitis (MPA) (9.5%). Proportion of RI in GPA, MPA, and EGPA accounted for 67.8%; 40.0%; 97.6%, respectively. The number of relapses was higher in the RI group (median 1.0 vs. 0.0; p=0.01). In the subgroup of combined GPA and MPA with RI, the trends toward higher proportion of deaths (11.7% vs. 5.7%; p=0.07), relapses requiring hospitalisation (52.2% vs. 42.4%, p=0.07) and relapses requiring admission to the intensive care unit (5.6% vs. 1.4%, p=0.09) were observed, median maximal concentration of CRP was higher (46 vs. 25 mg/l; p=0.01) and more aggressive treatment was administered. CONCLUSIONS: Prevalence of RI in the Polish population of AAV is similar to the values reported in the literature, however, the proportion observed in GPA is closer to those presented in Asian than Western European cohorts. RI seems to be associated with a more severe course of disease and its presence prompts more aggressive treatment.

Association of antineutrophil cytoplasmic antibody (ANCA) specificity with demographic and clinical characteristics of patients with ANCA­associated vasculitides.

INTRODUCTION: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is characterized by the presence of proteinase­3 (PR3) or myeloperoxidase (MPO) ANCA. In over 90% of cases, PR3­ANCA is associated with granulomatosis with polyangiitis (GPA). However, it is also rarely found in microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). On the other hand, MPO­ANCA being characteristic of MPA (>90% of cases), is also found in about 40% of EGPA and 5% of GPA patients. On the ground of this overlap, clinical importance of ANCA specificity identification has been questioned. OBJECTIVES: In this study, we analyzed the clinical and demographic characteristics of AAV subgroups identified by ANCA serotype. PATIENTS AND METHODS: We conducted a multicenter study of AAV patients (417 GPA, 106 MPA, 102 EGPA; diagnosed between 1990 and 2016), included in the POLVAS registry. The data were systematically collected according to a standardized protocol. RESULTS: In the ANCA-positive group (anti­MPO, anti­PR3) a male-to-female ratio was 1:1, whereas in the ANCA-negative group it was 1:2, regardless of AAV diagnosis. Anti­MPO antibodies were present in significantly older patients. Patients with MPO+GPA and MPO+EGPA were older than those with corresponding ANCA­negative GPA and EGPA as well as PR3+AAV. Moreover, ANCA­negative AAV was characterized by a low risk of end­stage kidney disease and death. CONCLUSIONS: The presence and specificity of ANCA in AAV patients are related to sex and age, determine their organ involvement and influence mortality as previously shown. Patients with MPO­ANCA-positive AAV constitute a clinically homogeneous group, whereas PR3­ANCA-positive patients are much more clinically heterogeneous. ANCA-negative AAV patients are characterized by better prognosis. Thus, ANCA identification is an indispensable element and should not be omitted in establishing AAV diagnosis.

Subphenotypes of ANCA-associated vasculitis identified by latent class analysis.

OBJECTIVES: ANCA-associated vasculitides (AAV) are a heterogeneous group of rare diseases with unknown aetiology and the clinical spectrum ranging from life-threatening systemic disease, through single organ involvement to minor isolated skin changes. Thus, there is an unmet need for phenotype identification, especially among patients with granulomatosis with polyangiitis (GPA). Patients with microscopic polyangiitis (MPA) seem to be clinically much more uniform. Recently, three subcategories of AAV have been proposed and described as non-severe AAV, severe PR3-AAV, and severe MPO-AAV. METHODS: In line with these attempts, we decided to use an unbiased approach offered by latent class analysis (LCA) to subcategorise GPA and MPA in a large cohort of Polish AAV patients included in a multicentre POLVAS registry. RESULTS: LCA of our AAV group identified a four-class model of AAV, including previously proposed three subphenotypes and revealing a fourth (previously not described) clinically relevant subphenotype. This new subphenotype includes only GPA patients, usually diagnosed at a younger age as compared to other groups, and characterised by multiorgan involvement, high relapse rate, relatively high risk of death, but no end-stage kidney disease. CONCLUSIONS: Based on multiple clinical and serological variables, LCA methodology identified 4-class model of AAV. This newly described fourth class of AAV may be of clinical relevance and may require prompt diagnosis and aggressive treatment due to the multiorgan involvement, high risk of relapse and marked mortality among these relatively young GPA subjects.

Treatment and its side effects in ANCA-associated vasculitides - Study based on POLVAS registry data.

PURPOSE: The aim of this study is to present the treatment modalities and associated side effects in a Polish nation-wide ANCA-associated vasculitides (AAV) patients' cohort. MATERIALS AND METHODS: Retrospective analysis of patients diagnosed with AAV between 1990 and 2016, included in the POLVAS registry was performed. Standard descriptive statistic methods were used with an emphasis on the treatment modalities. RESULTS: There were 625 patients diagnosed with AAV included in this study: 417 cases of granulomatosis with polyangiitis (GPA; 66.7%), 106 cases of microscopic polyangiitis (MPA; 17.0%) and 102 cases of eosinophilic granulomatosis with polyangiitis (EGPA; 16.3%). The mean age at the date of diagnosis was 50.4 (±15.7) years and the median observational period amounted to 4.0 (2.0-8.0) years. Glucocorticosteroids (GCs) were the medicaments most frequently used for remission induction (593/622; 95.3%), followed by cyclophosphamide (487/622; 78.3%), rituximab (44/622; 7.1%), and methotrexate (39/622; 6.3%). GCs were also most frequently administered for maintenance therapy (499/592; 84.3%), followed by azathioprine (224/592; 37.8%), methotrexate (136/592; 23.0%) and mycophenolate mofetil (99/592; 16.7%). The median cumulative doses of cyclophosphamide and rituximab equalled 7.99 g (4.18-14.0) and 2000 mg (1500-2800), respectively. The most commonly observed adverse events included: infections - 214/551 cases (38.8%), which were associated with the time of observation (OR = 1.05; 95% CI 1.01-1.10), the use of GCs intravenous pulses (OR = 2.76; 95% CI 1.68-4.54) and need for haemodialysis (OR = 1.73; 95% CI 1.10-2.71). CONCLUSIONS: Polish patients with AAV were predominantly treated according to appropriate guidelines. The most frequent adverse events were typical for usually administered immunosuppressive treatment.